CNOT1 p.Arg535Cys variant in holoprosencephaly with late onset diabetes mellitus
Amaro Freire de Queiroz Júnior1, Maria Teresa Vieira Sanseverino1,2, Marcus Vinicius Martins Collares3
1Serviço de Genética Médica, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil.
Abstract:
Holoprosencephaly (HPE) results from a lack of cleavage of the prosencephalon. It has a complex etiology, resulting from chromosome abnormalities or single gene variants in the Sonic hedgehog signaling pathway. A single variant, p.Arg535Cys in CNOT1, has been described in HPE in association with pancreatic agenesis and neonatal diabetes. Here, we report on a case of HPE and p.Arg535Cys in CNOT1 without pancreatic agenesis where the patient presented with diabetes mellitus in adolescence. This case reinforces the role of CNOT1 in pancreatic development. We suggest that individuals with p.Arg535Cys in CNOT1 with no pancreas abnormalities observed at birth should be screened for diabetes during follow-up.
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